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RNA Biol. 2014;11(2):124-33. doi: 10.4161/rna.27863. Epub 2014 Feb 5.

Sustained stabilization of Interleukin-8 mRNA in human macrophages.

Author information

1
Molecular Biomedicine Program; King Faisal Specialist Hospital and Research Center; Riyadh, Saudi Arabia.
2
Molecular Biomedicine Program; King Faisal Specialist Hospital and Research Center; Riyadh, Saudi Arabia; Department of Biochemistry; King Saud University; Riyadh, Saudi Arabia.
3
Department of Biochemistry; King Saud University; Riyadh, Saudi Arabia.

Abstract

The mRNAs of most inflammatory mediators are short-lived due to AU-rich elements (AREs) in their 3'-untranslated regions. AREs ensure a low basal level of expression during homeostasis and a transient nature of expression during the inflammatory response. Here, we report that the mRNA of the pro-inflammatory chemokine IL-8, which contains an archetypal ARE, is unexpectedly constitutively abundant and highly stable in primary human monocytes and macrophages. Using the pre-monocyte-like THP-1 cell line that can differentiate into macrophage-like cells, we show that a low level of unstable IL-8 mRNA in undifferentiated cells (half-life<30 min) becomes constitutively elevated and the mRNA is dramatically stabilized in differentiated THP-1 cells with a half-life of more than 15 h similar to primary monocytes and macrophages. In contrast, the level and stability of TNF-α mRNA also containing an ARE is only slightly affected by differentiation; it remains low and unstable in primary macrophages and differentiated THP-1 cells with an estimated half-life of less than 20 min. This differentiation-dependent stabilization of IL-8 mRNA is p38 MAPK-independent and is probably coupled with reduced protein translation. Reporter assays in THP-1 cells suggest that the ARE alone is not sufficient for the constitutive stabilization in macrophage-like cells and imply an effect of the natural biogenesis of the transcript on the stabilization of the mature form. We present a novel, cell type-dependent sustained stabilization of an ARE-containing mRNA with similarities to situations found in disease.

KEYWORDS:

AU-rich elements; CXCL-8; IL-8; mRNA stability; macrophages; monocytes

PMID:
24525793
PMCID:
PMC3973731
DOI:
10.4161/rna.27863
[Indexed for MEDLINE]
Free PMC Article

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